RESUMEN
Increased production of extracellular matrix is a necessary response to tissue damage and stress. In a normal healing process, the increase in extracellular matrix is transient. In some instances; however, the increase in extracellular matrix can persist as fibrosis, leading to deleterious alterations in organ structure, biomechanical properties, and function. Indeed, fibrosis is now appreciated to be an important cause of mortality and morbidity. Extensive research has illustrated that fibrosis can be slowed, arrested or even reversed; however, few drugs have been approved specifically for anti-fibrotic treatment. This is in part due to the complex pathways responsible for fibrogenesis and the undesirable side effects of drugs targeting these pathways. Natural products have been utilized for thousands of years as a major component of traditional medicine and currently account for almost one-third of drugs used clinically worldwide. A variety of plant-derived compounds have been demonstrated to have preventative or even reversal effects on fibrosis. This review will discuss the effects and the underlying mechanisms of some of the major plant-derived compounds that have been identified to impact fibrosis.
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Matriz Extracelular , Fitoquímicos , Humanos , Fibrosis , Matriz Extracelular/metabolismo , Fitoquímicos/farmacologíaRESUMEN
BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.
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Cardiomiopatía Chagásica/sangre , ADN Protozoario/sangre , Trypanosoma cruzi/genética , Adulto , Donantes de Sangre , Estudios de Casos y Controles , Cardiomiopatía Chagásica/parasitología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trypanosoma cruzi/patogenicidadRESUMEN
With rising patient volumes and increasingly complex cases, the specialty of emergency medicine faces a growing array of challenges. Efforts have been made to improve patient throughput, yet little attention has been directed to the increasing amount of primary care delivered in emergency departments (EDs) for chronic disease states such as hypertension and diabetes. Management of chronic medical conditions is traditionally seen as beyond the purview of the ED and emergency physicians tend to defer critical aspects of related patient care to other components of the healthcare continuum. As a result, vulnerable patients are often forced to navigate exceedingly complex and fragmented systems of care with little guidance, which often leads to inadequate treatment and exposure to increased risk for development of potentially avoidable complications. As evidenced by our experience with hypertension in an under resourced community, there is a crucial need for emergency physicians to espouse their role as providers of healthcare across the acuity spectrum and lead the way in defining regionally relevant solutions to better manage patients with chronic medical problems.
RESUMEN
BACKGROUND: Although risk factors for HIV infection are known, it is important for blood centres to understand local epidemiology and disease transmission patterns. Current risk factors for HIV infection in blood donors in Brazil were assessed. METHODS: A case-control study was conducted at large public blood centres located in four major cities between April 2009 and March 2011. Cases were persons whose donations were confirmed positive by enzyme immunoassays followed by Western blot confirmation. Audio computer-assisted structured interviews (ACASI) were completed by all cases and controls. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs). RESULTS: There were 341 cases, including 47 with recently acquired infection, and 791 controls. Disclosed risk factors for both females and males were sex with an HIV-positive person AOR 11.3, 95% CI (4.1, 31.7) and being an IVDU or sexual partner of an IVDU [AOR 4.65 (1.8, 11.7)]. For female blood donors, additional risk factors were having male sex partners who also are MSM [AOR 13.5 (3.1, 59.8)] and having unprotected sex with multiple sexual partners [AOR 5.19 (2.1, 12.9)]. The primary risk factor for male blood donors was MSM activity [AOR 21.6 (8.8, 52.9)]. Behaviours associated with recently acquired HIV were being a MSM or sex partner of MSM [13.82, (4.7, 40.3)] and IVDU [11.47, (3.0, 43.2)]. CONCLUSION: Risk factors in blood donors parallel those in the general population in Brazil. Identified risk factors suggest that donor compliance with selection procedures at the participating blood centres is inadequate.
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Donantes de Sangre , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , VIH-1 , Auditoría Médica , Adolescente , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Infecciones por VIH/prevención & control , Humanos , Masculino , Factores de Riesgo , Asunción de Riesgos , Sexo InseguroRESUMEN
BACKGROUND AND OBJECTIVE: Previous studies have shown that volunteer, community-recruited donors have a higher prevalence of human immunodeficiency virus (HIV) infection in São Paulo, Brazil, than replacement donors. One hypothesis which may explain this unexpected finding is that some individuals donate blood because they are seeking HIV testing. The objective of this study was to characterize test-seeking blood donors and to determine whether they are at higher risk for HIV infection compared with other donors. MATERIALS AND METHODS: Subjects presenting for blood donation were asked to participate in a study assessing their motivations (including test seeking) to donate, as measured by perceiving donation as a means to obtain infectious disease test results. Participants completed the standard blood bank predonation screening questions plus our additional survey, and were tested for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphocytotrophic virus (HTLV) I/II, syphilis and Chagas' disease. As a result of anticipated low statistical power to directly measure the association between test-seeking motivation and HIV infection, we tested for herpes simplex virus type 2 (HSV-2) as a marker of sexual risk for HIV. Our survey includes accepted donors as well as persons whose risk-behaviour histories would result in their exclusion from donation according to routine screening procedures. RESULTS: Of 1,720 potential blood donors randomly selected and approached, 1,600 (93.0%) participated. Overall, 141 (8.8%) were classified as test seekers; 15.6% of these were HSV-2 positive. The proportion of test seekers was the same among community-recruited and replacement donors. Test seekers had a higher prevalence of HSV-2 [adjusted odds ratio (AOR) 1.66; 95% confidence interval (CI): 1.06-2.59] adjusting for age, gender and prior donation. The association was significant among community-recruited blood donors whose previous donation was more than 1 year ago (i.e. 'lapsed donors') (AOR 2.55; 95% CI: 1.20-5.44). Test seekers were not more likely to be rejected from blood donation as a result of health reasons, self-reported HIV risk-related behaviour, or by their own confidential unit exclusion. We found no difference in HSV-2 prevalence between persons accepted for donation (15.7%) and those rejected because of self-reported sexual risk (16.7%). CONCLUSIONS: We did not detect a difference in the proportion of test seekers across different types of blood donors; however, we did detect an association between HSV-2 infection and test seeking, especially among community-recruited lapsed blood donors. Of note, questions on test-seeking behaviour detected donors with increased prevalence of HSV-2, but the self-reported sexual risk behaviours currently used for deferral criteria did not. Incentives to get tested at sites other than blood banks may decrease the residual risk of HIV in the blood supply.
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Donantes de Sangre , Infecciones por VIH/sangre , VIH , Intención , Tamizaje Masivo , Adulto , Donantes de Sangre/psicología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Humanos , Masculino , Tamizaje Masivo/psicología , Factores de RiesgoRESUMEN
In order to gain new insights into the risk factors influencing human-T-cell-leukemia/lymphoma-virus-type-I (HTLV-I) mother-to-child transmission, a retrospective study of HTLV-I infection among children born to HTLV-I-seropositive women was carried out in a highly HTLV-I-endemic population of African origin living in French Guyana. The study covered 81 HTLV-I-seropositive mothers and their 216 children aged between 18 months old and 12 years old. All plasma samples were tested for the presence of HTLV-I antibodies by ELISA, immunofluorescence assay and Western blot. HTLV-I provirus was detected, in the DNA extracted from peripheral-blood mononuclear cells, by polymerase chain reaction (PCR) using primers specific for 3 different HTLV-I genomic regions (LTR, gag and pX) and quantified by a competitive PCR assay. Out of the 216 children, 21 were found to be HTLV-I-seropositive, giving a crude HTLV-I transmission rate of 9.7%, while among the 180 breast-fed children 10.6% were HTLV-I-seropositive. Perfect concordance between serological and PCR results was observed, and none of the 195 HTLV-I-negative children was found HTLV-I-positive by PCR. In conditional (by family) logistic-regression models, HTLV-I seropositivity in children was associated with an elevated maternal anti-HTLV-I-antibody titer (OR 2.2, p = 0.0013), a high maternal HTLV-I proviral load (OR 2.6, p = 0.033) and child's gender, girls being more frequently HTLV-I-infected than boys: OR 3.6, p = 0.0077 in the model including maternal anti-HTLV-I-antibody titer and OR 4.1, p = 0.002 in the model including the maternal HTLV-I proviral load.
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Portador Sano/virología , Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/transmisión , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/virología , Lactancia Materna , Niño , Preescolar , ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Guyana Francesa , Genoma Viral , Infecciones por HTLV-I/sangre , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Lactante , Recién Nacido , Masculino , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Provirus/genética , Provirus/aislamiento & purificación , Estudios Retrospectivos , Carga ViralRESUMEN
We studied plasma samples from 2082 Mataco Indians living in 22 different communities in the western part of Formosa Province, northern Argentina. Samples were screened for HTLV-I/II antibodies by particle agglutination assay. All positive or borderline samples were then tested by an immunofluorescence assay (IFA) on C19 HTLV-II-producing cells. Western blot was used for confirmation of all IFA-positive plasma samples. The crude HTLV-II seroprevalence was 3.0% (62 of 2051), and 0.9% (5 of 588) in children less than 10 years old. The latter result suggests ongoing mother-to-child transmission, probably by breast feeding. There was a marked increase in HTLV-II seroprevalence with age (0.9%, 0-10 years; 1.6%, 11-20 years; 4.4%, 21-30 years; 3.4%, 31-40 years; 7.2%, 41-50 years; 5.7%, >50 years) in both male (p = 0.002) and female subjects (p = 0.00002). None of the 80 non-Indian inhabitants tested was HTLV-I/II seropositive. In a second study, among 105 Toba Indians from a village (Primavera) of the eastern part of this region, 23 were HTLV-II seropositive with a seroprevalence of 59% in those more than 40 years old. From seven of the Indians from Primavera, three others from neighboring regions (including two Tobas and one Pilaga), and one intravenous drug user (IVDU) from Rosario, DNA was extracted from peripheral blood mononuclear cells, and the gp21 transmembrane-encoding gene (590 bp) was amplified by PCR, cloned, and sequenced. LTR sequences were also obtained from the Pilaga, the IVDU, and one Toba. Molecular and phylogenetic analyses revealed that the Indians were all infected with closely related HTLV-II molecular strains belonging to the b subtype, while the IVDU was infected with an HTLV-II subtype a variant. Such data help to make a phylogenetic atlas of HTLV-II among Amerindian tribes and are crucial to gain new insights into the origin and modes of dissemination of this human retrovirus in the Americas.
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Infecciones por HTLV-II/epidemiología , Virus Linfotrópico T Tipo 2 Humano/genética , Indígenas Sudamericanos , Adolescente , Adulto , Distribución por Edad , Argentina/epidemiología , Niño , Preescolar , Anticuerpos Antideltaretrovirus/sangre , Femenino , Técnica del Anticuerpo Fluorescente , Genes env , Infecciones por HTLV-II/transmisión , Virus Linfotrópico T Tipo 2 Humano/aislamiento & purificación , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Estudios Seroepidemiológicos , Distribución por Sexo , Secuencias Repetidas Terminales/genéticaRESUMEN
To determine the epidemiological characteristics of human T cell leukemia/lymphoma virus type I (HTLV-I) infection in the endemic village of Maripasoula, French Guiana, 1,614 persons (83.2% of the population) aged 2 to 91 years (mean age 21) were studied from November 1994 through April 1995. Plasma samples were screened by an HTLV-I ELISA and an IFA test (on MT2 cells), and positive samples were tested by an HTLV-I and -II type-specific Western blot. Overall seropositivity in the village was 6.7%, but HTLV-I infection was restricted to 3 of 6 ethnic groups, including the Noir-Marron (descendants of escaped African slaves, 8%), the Creoles (4.1%) and those of mixed Noir Marron/other ethnicity (3.6%). In the Noir-Marron population of 1,222 persons, including 606 men and 616 women and representing 76% of those tested, HTLV-I seroprevalence increased significantly with age in both sexes, reaching 40% in women older than 50 years. Univariate risk factors for HTLV-I seropositivity in women included older age, more pregnancies, more live births and a history of hospitalization. A cross-sectional analysis of sexual partners demonstrated an excess of discordant female HTLV-I+/male HTLV-I- couples, indicating preferential male-to-female sexual transmission. The demonstration of II HTLV-I-seropositive children aged less than 15 years, of whom 9 had a seropositive mother, suggested maternal-child HTLV-I transmission. Our results demonstrate a very high seroprevalence of HTLV-I in this South American population descended from African slaves, probably due to high rates of mother-to-child and sexual transmission within this rather isolated group.
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Enfermedades Endémicas , Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Guyana Francesa/epidemiología , Infecciones por HTLV-I/etnología , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/transmisión , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Regresión , Enfermedades de Transmisión Sexual/inmunologíaRESUMEN
BACKGROUND: We investigated behavioural and environmental risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I). METHODS: A nested case-control study of 201 HTLV-I seropositive subjects and 225 age- and sex-matched seronegative controls was performed using questionnaire data from the enrollment visit of a cohort study in 1987-1988. HTLV-I serostatus was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot. RESULTS: Among women, the number of lifetime sexual partners (P < 0.05, chi 2 trend) and the number of different men fathering a child by the woman (P < 0.06, chi 2 trend) were associated with HTLV-I seropositivity. Use by the female subject of an intrauterine device (IUD) was associated with an increased risk of seropositivity (odds ratio (OR) = 2.67, 95% confidence interval (CI): 1.13-6.23); condom use was rare in this population. Among male subjects, a larger number of lifetime sexual partners was also associated with HTLV-I seropositivity (P < 0.05, chi 2 trend). No association was found between HTLV-I seropositivity and educational attainment, income, or occupation. Having been breastfed as a child or receipt of a blood transfusion had elevated but imprecise OR due to very high and low prevalence of the risk factors, respectively. Several variables relating to insect or animal exposure showed no association with HTLV-I seropositivity. CONCLUSIONS: These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.
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Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano , Enfermedades de Transmisión Sexual/epidemiología , Adulto , Western Blotting , Estudios de Casos y Controles , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos Anti-HTLV-I/análisis , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/transmisión , Humanos , Jamaica/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Seroepidemiológicos , Parejas Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND: Other than adult T-cell leukaemia (ATL) and HTLV-I associated myelopathy (HAM), the health effects of infection with human T-lymphotropic virus type I (HTLV-I) are not well defined. METHOD: A cohort of 201 confirmed HTLV-I seropositive Jamaican food service workers and 225 seronegative controls of similar age and sex from the same population was examined. A health questionnaire, physical examination, and laboratory tests were performed at enrollment into the cohort in 1987-1988. RESULTS: One of 201 HTLV-I seropositives, but no controls were diagnosed with HAM, for a prevalence of 0.5% (95% confidence interval) (CI) 0.01-2.7%); no cases of ATL were diagnosed. While there was no difference in current symptoms, the HTLV-I seropositive group was more likely to report a past medical history of hepatitis or jaundice (OR = 3.49, 95% CI: 0.93-13.08), malaria (OR = 2.13, 95% CI: 0.96-4.73), and dengue fever (OR = 1.37, 95% CI: 0.82-2.29); however, these differences were of borderline statistical significance. Low income HTLV-I seropositive women had lower body weight (P < 0.01) and body mass index (P < 0.009) than their seronegative counterparts; similar differences were seen in the smaller male group. A trend toward higher prevalence of severe anaemia (haemoglobin < 10 g/dl) (12.6% versus 7.7%, P < 0.105) and a significantly lower prevalence of eosinophilia (1.0% versus 6.3%, P < 0.004) was seen among HTLV-I seropositives compared to controls. CONCLUSIONS: Although most HTLV-I seropositives are asymptomatic, HAM may be diagnosed in approximately 0.5% of carriers. Chronic HTLV-I infection may also exert subtle effects on body mass and haematological parameters.
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Paraparesia Espástica Tropical/complicaciones , Adulto , Anemia/sangre , Anemia/epidemiología , Anemia/etiología , Índice de Masa Corporal , Estudios de Cohortes , Eosinofilia/sangre , Eosinofilia/epidemiología , Eosinofilia/etiología , Eosinófilos/inmunología , Femenino , Humanos , Jamaica/epidemiología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/sangre , Paraparesia Espástica Tropical/epidemiología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
Human T-cell lymphotropic virus type I (HTLV-I) has been etiologically associated with a neurologic syndrome called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-I infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-I-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-I seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-I seropositive compared with two (4.0%) of the controls with other neurologic diseases. Given HTLV-I seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual confidence interval 1.29-12.46 for individuals aged < or = 15; odds ratio = 4.26, 95% confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95% confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse or the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-I infection, whereas adult T-cell leukemia/lymphoma is not.
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Paraparesia Espástica Tropical/epidemiología , Enfermedades Virales de Transmisión Sexual/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Jamaica/epidemiología , Leucemia-Linfoma de Células T del Adulto/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/inmunología , Paraparesia Espástica Tropical/transmisión , Estudios Retrospectivos , Factores de Riesgo , Pruebas Serológicas , Conducta Sexual , Enfermedades Virales de Transmisión Sexual/inmunologíaRESUMEN
To study mother-to-child transmission of HTLV-I in Jamaica, we screened antenatal patients in Kingston, Jamaica, from 1983 to 1985. Of 2,329 women, 81 (3.5%) were HTLV-I seropositive. Two to three years later, 36 seropositive mothers were recontacted, and blood was drawn from them and their children. All sera were tested for HTLV-I antibodies, and mother's sera were additionally tested for HTLV-I whole-virus antibody titer, syncytium-inhibition neutralizing antibody titer, and titers to six synthetic peptides from the HTLV-I envelope glycoprotein gp46. Seventeen of 74 (23%) [95% confidence interval (CI) 15-34%] children were seropositive. HTLV-I transmission was associated with breast-feeding duration > 6 months [relative risk (RR) 3.2; CI 0.4-22.1], maternal age > 30 years (RR 2.8; CI 1.0-7.8), and higher maternal whole-virus antibody titer (RR 3.3; CI 1.3-8.5). After controlling for higher whole-virus antibody titer, transmission remained associated with higher titer of neutralizing antibody and higher titer of antibody to the peptide sp4a1, corresponding to amino acids 196-209 of the gp46 envelope glycoprotein. We conclude that mother-to-child transmission of HTLV-I in Jamaica is associated with longer duration of breast-feeding, older age, and higher HTLV-I antibody titer, in particular to a certain immunogenic portion of the gp46 envelope glycoprotein.
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Productos del Gen env/inmunología , Anticuerpos Anti-HTLV-I/sangre , Antígenos HTLV-I/inmunología , Infecciones por HTLV-I/transmisión , Proteínas Oncogénicas de Retroviridae/inmunología , Adolescente , Lactancia Materna , Niño , Preescolar , Epítopos/inmunología , Femenino , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/inmunología , Humanos , Lactante , Recién Nacido , Jamaica/epidemiología , Edad Materna , Embarazo , Factores de RiesgoRESUMEN
The 2.55 kb Staphylococcus aureus plasmid, pRJ5, confers constitutive resistance to macrolide-lincosamide-streptogramin B (MLS) antibiotics. pRJ5 is nearly identical to the inducible MLS resistance plasmid pT48, and has homology with the S. aureus plasmids pE194 and pSN2. The HindIII-C and/or Hind-B fragments were required for stable maintenance of the plasmid and probably carry palA. Plasmids pRJ5 and pT48 were shown to belong to the same incompatibility group, Inc12 (L). DNA sequencing showed that pRJ5 contains a 28 bp direct tandem duplication in the leader/attenuator region of ermC. This is likely to change the secondary structure of the methylase mRNA, allowing constitutive expression of ermC. The type of mutation found on plasmid pRJ5 is different from those observed in similar 2.5 kb constitutive MLS-resistance plasmids isolated from other Gram-positive bacteria, including staphylococci.
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Antibacterianos/farmacología , Macrólidos , Familia de Multigenes , Plásmidos/genética , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)/genética , Staphylococcus aureus/genética , Secuencia de Bases , Farmacorresistencia Microbiana , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos/genética , Lincosamidas , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Secuencias Reguladoras de Ácidos Nucleicos/genética , Virginiamicina/farmacologíaRESUMEN
To evaluate the risk of transfusion-related transmission of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I-negative transfusion recipients at monthly intervals post-transfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immuno-suppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible.
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Anticuerpos Anti-HTLV-I/análisis , Infecciones por HTLV-I/transmisión , Reacción a la Transfusión , Donantes de Sangre , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/epidemiología , Humanos , Jamaica/epidemiología , Prevalencia , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
A subsample (1.6%; n = 13,260) of a healthy Jamaican population of food-handlers, studied by Murphy et al. (1991), who were serologically positive (n = 99) or negative (n = 113) for HTLV-I was investigated for intestinal parasitic infection using coprological methods. Helminth infection included Ascaris lumbricoides (2.8%), Trichuris trichiura (7.1%) and hookworms (6.1%). Entamoeba coli was found in 21.8% of samples, while E. hartmanni, Giardia lamblia, Endolimax nana, Iodamoeba bütschlii and Chilomastix mesnili each occurred in less than 10% of responders. T. trichiura displayed a higher prevalence (10.6 vs 3%) (chi 2 = 4.623; P = 0.03) in the HTLV-I negative group. G. lamblia was detected more frequently among HTLV-I carriers compared to controls (9.1 and 3.5%, respectively), but the association was not statistically significant (chi 2 = 2.825; P = 0.09). Infection with intestinal parasites is likely to occur independent of HTLV-I status: however, possible HTLV-I-induced immunosuppression may lead to higher intensity infections of certain organisms thus facilitating easier detection using parasitological methods. The immunomodulatory potential of HTLV-I infection in the aetiology of non-malignant diseases requires further investigation.
Asunto(s)
Portador Sano , Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/complicaciones , Parasitosis Intestinales/complicaciones , Infecciones por Nematodos/complicaciones , Infecciones por Protozoos/complicaciones , Análisis de Varianza , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Humanos , Parasitosis Intestinales/epidemiología , Jamaica/epidemiología , Masculino , Infecciones por Nematodos/epidemiología , Prevalencia , Infecciones por Protozoos/epidemiologíaRESUMEN
During 1985 and 1986, the authors measured antibodies to human T-lymphotropic virus type I (HTLV-I) in a cohort of 13,260 Jamaicans from all parts of the island who applied for food-handling licenses. HTLV-I seroprevalence was strongly age and sex dependent, rising from 1.7% (10-19 years) to 9.1% (greater than or equal to 70 years) in men and from 1.9% (10-19 years) to 17.4% (greater than or equal to 70 years) in women. In a logistic regression analysis, women were more likely to be seropositive than were men, and farmers, laborers, and the unemployed were more likely to be HTLV-I seropositive than were those reporting student or professional occupations. In men, African ethnicity was associated with HTLV-I seropositivity in the univariate analysis but was not a risk factor after adjustment for age and sex. There was a trend toward higher age-stratified HTLV-I seroprevalence among younger women who reported more pregnancies, but older multigravidas had lower rates of HTLV-I seropositivity. Persons born outside Jamaica had significantly lower seroprevalence than did those born in Jamaica, but they were of slightly different ethnic and occupational compositions than those born in Jamaica.
Asunto(s)
Anticuerpos Anti-HTLV-I/análisis , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Análisis por Conglomerados , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos Anti-HTLV-I/inmunología , Humanos , Jamaica , Masculino , Persona de Mediana Edad , Factores Sexuales , Encuestas y CuestionariosRESUMEN
An island-wide cohort of 13,260 Jamaicans who applied for food-handling licenses during 1985 and 1986 were tested for antibodies to human T-cell lymphotropic virus type I (HTLV-I). Demographic and residence history data were linked to geographic and ecologic measures of elevation, rainfall, crop-growing areas, population density, and additional measures of urbanization and correlated with HTLV-I antibody status. By logistic regression analysis (performed separately for men and women), men and women who currently resided at low elevation (less than or equal to 1,000 ft (305 m)) were more likely to be HTLV-I infected than were those residing at high elevation. Men, but not women, who were born in citrus-growing areas were more likely to be HTLV-I infected than were men who were born in other areas. By univariate analysis, there was a significant positive trend of increasing HTLV-I seroprevalence with increasing amount of annual rainfall associated with birthplace and primary residence areas. However, these associations did not remain significant after adjusting for age and sex. These environmental associations raise the possibility of new modes of viral transmission or host response to infection, although they may simply be surrogates for socioeconomic status, breastfeeding habits, or sexual behavior, which are known determinants of HTLV-I zero prevalence.
Asunto(s)
Anticuerpos Anti-HTLV-I/análisis , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Densidad de Población , Adolescente , Adulto , Anciano , Altitud , Niño , Ecología , Femenino , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Jamaica/epidemiología , Masculino , Persona de Mediana Edad , Lluvia , Análisis de RegresiónRESUMEN
From a cohort of human T-cell lymphotropic virus type I (HTLV-I) exposed transfusion recipients (N = 71) enrolled in the Jamaican Transfusion Study, 11 were selected for detailed laboratory evaluation. All recipients were followed at monthly intervals for 6 months and then bimonthly up to 1 year for evidence of HTLV-I seroconversion. Without regard to results on screening assays, pretransfusion and posttransfusion samples were tested with two licensed HTLV-1 whole-virus screening enzyme immunoassays (EIAs), recombinant EIAs for antibody against tax (p40x) and p21e envelope, standard whole virus Western blot (WB), WB enhanced with recombinant p21e, and radioimmunoprecipitation assay (RIPA). In the early period posttransfusion, antibody to gag core protein was predominant with anti-p24 generally appearing before anti-p19. Recombinant anti-p21e envelope protein, in EIA and WB format, was frequently the earliest envelope reactivity detected, while anti-gp46 in WB and anti-gp61/68 in RIPA system appeared later. Anti-tax antibodies appeared later in the time course of seroconversion. The whole-virus EIAs were less sensitive than the confirmatory assays. The combination of WB and RIPA or WB enhanced with recombinant p21e appeared equally effective in confirming samples as positive by the Public Health Service two gene group confirmatory algorithm. However, specificity of this assay approach could not be addressed in this study.
Asunto(s)
Transfusión Sanguínea , Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/transmisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/inmunología , Western Blotting , Femenino , Productos del Gen env/inmunología , Productos del Gen gag/inmunología , Productos del Gen tax/inmunología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Técnicas para Inmunoenzimas , Jamaica , Masculino , Proteínas Recombinantes/inmunología , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
STUDY OBJECTIVE: To study the seroprevalence of human T-lymphotropic virus type I (HTLV-I) in a sexually active population and to determine sexual behavior risk factors for infection. DESIGN: Cross-sectional seroprevalence study using enzyme-linked immunosorbent assay (ELISA) and Western blot. Risk-factor data were gathered by administered questionnaire and chart review. SETTING: Two urban, primary care clinics for persons with sexually transmitted diseases run by the Jamaican Ministry of Health. PATIENTS: Of the 2050 consecutive patients presenting with new episodes of sexually transmitted disease, 1977 patients were eligible for analysis. MEASUREMENTS AND RESULTS: Overall HTLV-I seroprevalence was 5.7%; prevalence increased with age from 1.6% (age, 14 to 19 years) to 5.1% (age, 30 years and older) in men and from 5.3% (age, 14 to 19 years) to 14.1% (age, 30 years and older) in women. Compared with a reference cohort of food service employees, age-adjusted HTLV-I seroprevalence was increased in female patients with sexually transmitted disease (odds ratio = 1.83; CI, 1.41 to 2.83) but not in male patients with sexually transmitted disease. Independent risk factors for HTLV-I infection in women included having had more than ten lifetime sexual partners (odds ratio = 3.52, CI, 1.28 to 9.69) and a current diagnosis of syphilis (odds ratio = 2.12; CI, 1.12 to 3.99). In men, a history of penile sores or ulcers (odds ratio = 2.13; CI, 1.05 to 4.33) and a current diagnosis of syphilis (odds ratio = 3.56; CI, 1.24 to 10.22) were independent risk factors for HTLV-I infection. Of 1977 patients, 5 (0.3%) had antibodies to human immunodeficiency virus type 1 (HIV-1), including 2 with HTLV-I and HIV-1 coinfection. CONCLUSIONS: We conclude that HTLV-I is transmitted from infected men to women during sexual intercourse. Our data are consistent with the lower efficiency of female-to-male sexual transmission of HTLV-I, but penile ulcers or concurrent syphilis may increase a man's risk of infection.